Design, Synthesis, and Evaluation of Chalcone Derivatives as Multifunctional Agents against Alzheimer's Disease

Wang, Xiaoqin; Zhou, Luyi; Tan, Ren-Xian; Liang, Guopeng; Fang, Si-Xian; Li, Wei; Xie, Mei; Wen, Yang; Wu, Jia‐Qiang

doi:10.1002/cbdv.202100341

Cited by 14 publications

(5 citation statements)

References 62 publications

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“…In studies examining the AD inhibitory effects of Cuchalcone complexes in the literature, it has been observed that complex structures are more effective. [59] However, while structures carrying fluorine atoms are less common, the effects of complex structures are noteworthy. These findings are consistent with our results and demonstrate similarities between the activities of Cu complexes in structures carrying halogens.…”

Section: Discussionmentioning

confidence: 99%

Investigation of Some Metabolic Enzyme Inhibition Properties of Novel Chalcone‐Cu Complexes

Ebiri,

Turgut,

Aktas Anil

et al. 2024

ChemistrySelect

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Fourteen novel Chalcone‐Cu complexes were effectively synthesized in this work. The newly synthesized Chalcone‐Cu complexes were assessed for their effects on human carbonic anhydrase isoenzymes I and II, acetylcholinesterase enzymes, and antioxidant activity. The intricate compounds exhibited Ki values ranging from 41.65–190.42 nM against hCA I, 15.79–259.07 nM against hCA II, and 14.36–175.73 nM against AChE enzymes. These complexes demonstrated potent inhibitory profiles against the specified metabolic enzymes, surpassing the inhibitory effects of acetazolamide (for hCA I and II) and tacrine (for AChE). The antioxidant properties of the compounds were assessed using DPPH and ABTS radical scavenging assays, revealing that the complexes had moderate to high efficacy in neutralizing free radicals. All complexes underwent molecular docking experiments. Compounds 14, 22, and 23 yielded the highest docking scores. Compound 14 demonstrated a docking score of −6.414 kcal/mol against hCAI, whereas compound 23 attained a docking score of −6.697 kcal/mol against hCA II. Compound 22 exhibited the most favorable docking score of −9.645 kcal/mol against AChE. The acquired results have the potential to help towards the development of new drugs containing Cu complex structures for the treatment of prevalent ailments such as glaucoma and Alzheimer's diseases.

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Section: Discussionmentioning

confidence: 99%

Investigation of Some Metabolic Enzyme Inhibition Properties of Novel Chalcone‐Cu Complexes

Ebiri,

Turgut,

Aktas Anil

et al. 2024

ChemistrySelect

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“…The Cu 2+− chelating properties of these compounds contribute to their ability to inhibit assembly and disaggregation of Aβ fibrils. The most active derivative (3 g) had low cytotoxicity, significantly reversed Aβ 1−42 -induced SH-SY5Y cell damage and ameliorated scopolamine-induced memory impairment in mice [331].…”

Section: -Hydroxy-chalcones and Bis-chalcone Ether Derivativesmentioning

confidence: 96%

Natural and Semi-Synthetic Flavonoid Anti-SARS-CoV-2 Agents for the Treatment of Long COVID-19 Disease and Neurodegenerative Disorders of Cognitive Decline

Melrose¹,

Smith²

2022

Front. Biosci. (Elite Ed)

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The aim of this review is to highlight the beneficial attributes of flavonoids, a diverse family of widely-distributed polyphenolic phytochemicals that have beneficial cell and tissue protective properties. Phytochemicals are widely distributed in plants, herbs and shrubs used in traditional complimentary medical formulations for centuries. The bioactive components that convey beneficial medicinal effects in these complex herbal preparations are now being identified using network pharmacology and molecular docking procedures that identify their molecular targets. Flavonoids have anti-oxidant, anti-inflammatory, antiviral, antibacterial and anti-cancer properties that have inspired the development of potent multifunctional derivatised flavonoids of improved efficacy. The antiviral properties of flavonoids and the emergence of the severe acute respiratory syndrome (SARS-CoV-2) pandemic has resulted in a resurgence of interest in phytochemicals in the search for efficacious compounds that can prevent viral infection or replication, with many promising plant compounds identified. Promising semi-synthetic flavonoid derivatives have also been developed that inhibit multiple pathological neurodegenerative processes; these offer considerable promise in the treatment of diseases of cognitive decline. Clinical trials are currently being undertaken to evaluate the efficacy of dietary supplements rich in flavonoids for the treatment of virally-mediated diseases. Such trials are expected to identify flavonoids with cell and tissue protective properties that can be harnessed in biomedical applications that may serve as supportive adjunctive procedures to conventional anti-viral drug therapies against diseases such as COVID-19.

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“…Apart from its Nrf2 activation capabilities, Lico-A also demonstrates direct antioxidant activity by effectively scavenging free radicals including superoxide anions, hydroxyl radicals, and hydrogen peroxide [ 122 ]. Furthermore, Lico-A exhibits the capacity to chelate transition metals like iron and copper, which are recognized catalysts for the generation of highly reactive ROS [ 123 ]. This chelation action helps prevent the formation of damaging oxidative species.…”

Section: Licochalcone A: a Natural Compound With A Multitarget Sidementioning

confidence: 99%

Licochalcone A: A Potential Multitarget Drug for Alzheimer’s Disease Treatment

Olloquequi,

Ettcheto,

Cano

et al. 2023

IJMS

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Licochalcone A (Lico-A) is a flavonoid compound derived from the root of the Glycyrrhiza species, a plant commonly used in traditional Chinese medicine. While the Glycyrrhiza species has shown promise in treating various diseases such as cancer, obesity, and skin diseases due to its active compounds, the investigation of Licochalcone A’s effects on the central nervous system and its potential application in Alzheimer’s disease (AD) treatment have garnered significant interest. Studies have reported the neuroprotective effects of Lico-A, suggesting its potential as a multitarget compound. Lico-A acts as a PTP1B inhibitor, enhancing cognitive activity through the BDNF-TrkB pathway and exhibiting inhibitory effects on microglia activation, which enables mitigation of neuroinflammation. Moreover, Lico-A inhibits c-Jun N-terminal kinase 1, a key enzyme involved in tau phosphorylation, and modulates the brain insulin receptor, which plays a role in cognitive processes. Lico-A also acts as an acetylcholinesterase inhibitor, leading to increased levels of the neurotransmitter acetylcholine (Ach) in the brain. This mechanism enhances cognitive capacity in individuals with AD. Finally, Lico-A has shown the ability to reduce amyloid plaques, a hallmark of AD, and exhibits antioxidant properties by activating the nuclear factor erythroid 2-related factor 2 (Nrf2), a key regulator of antioxidant defense mechanisms. In the present review, we discuss the available findings analyzing the potential of Lico-A as a neuroprotective agent. Continued research on Lico-A holds promise for the development of novel treatments for cognitive disorders and neurodegenerative diseases, including AD. Further investigations into its multitarget action and elucidation of underlying mechanisms will contribute to our understanding of its therapeutic potential.

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Design, Synthesis, and Evaluation of Chalcone Derivatives as Multifunctional Agents against Alzheimer's Disease

Cited by 14 publications

References 62 publications

Investigation of Some Metabolic Enzyme Inhibition Properties of Novel Chalcone‐Cu Complexes

Investigation of Some Metabolic Enzyme Inhibition Properties of Novel Chalcone‐Cu Complexes

Natural and Semi-Synthetic Flavonoid Anti-SARS-CoV-2 Agents for the Treatment of Long COVID-19 Disease and Neurodegenerative Disorders of Cognitive Decline

Licochalcone A: A Potential Multitarget Drug for Alzheimer’s Disease Treatment

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